A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD)

• Register: ClinicalTrials.gov
• Last refreshed on: 6 January 2025
• Main ID: NCT04849741
• Date of registration: 16/04/2021
• Prospective Registration: Yes
• Primary sponsor: Ionis Pharmaceuticals, Inc.
• Public title: A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD)
• Scientific title: A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients With Alexander Disease
• Date of first enrolment: June 1, 2021
• Target sample size: 73
• Recruitment status: Enrolling by invitation
• URL: https://clinicaltrials.gov/ct2/show/NCT04849741
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Australia, Canada, Israel, Italy, Japan, Netherlands, United Kingdom, United States

Key inclusion & exclusion criteria

Key Inclusion Criteria:

1. Clinical phenotype and brain imaging consistent with a diagnosis of Alexander
disease

2. Documented genetic mutation in the GFAP gene

3. Aged = 2 to 65 years old at the time of informed consent

4. Able and willing to meet all study requirements, including travel to Study Center,
procedures, measurements and visits

5. Patients < 18 years old at Screening must have a trial partner (parent, caregiver or
other)

Key Exclusion Criteria:

1. Clinically significant abnormalities in medical history or physical examination

2. Any clinically significant laboratory abnormalities that would render a patient
unsuitable for inclusion

3. Any contraindication or unwillingness to undergo MRI

4. Treatment with another investigational drug, biological agent, or device within 1
month of Screening, or 5 half-lives of investigational agent, whichever is longer;
concurrent participation in any other clinical study (including observational and
non-interventional studies)

5. Previous treatment with an oligonucleotide (including small interfering ribonucleic
acid [siRNA]) within 4 months of Screening if single dose received, or within 12
months of Screening if multiple doses received. This exclusion does not apply to
vaccines (both messenger ribonucleic acid [mRNA] and viral vector vaccines).

6. History of gene therapy or cell transplantation or any other experimental brain
surgery [ROW]

7. Obstructive hydrocephalus

8. Presence of a functional ventriculoperitoneal shunt for the drainage of
cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter

9. Known brain or spinal disease that would interfere with the lumbar puncture (LP)
process, CSF circulation or safety assessment.

10. Hospitalization for any major medical or surgical procedure involving general
anesthesia within 12 weeks prior to Screening or planned during the study

11. Have any other conditions, which, in the opinion of the Investigator would make the
patient unsuitable for inclusion, or could interfere with the patient participating
in or completing the study


Age minimum: 2 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alexander Disease

Intervention(s)

Drug: Placebo

Drug: zilganersen

Primary Outcome(s)

Percent Change from Baseline in the 10-Meter Walk Test (10MWT) [Time Frame: Baseline and Week 61]

Secondary Outcome(s)

Change From Baseline in 9-Hole Peg Test (9HPT) Score [Time Frame: Baseline to Week 61]

Change From Baseline in Patient Global Impression of Change (PGIC) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Pediatrics Quality of Life Inventory Gastrointestinal Symptoms Scale (PedsQL GI) Score [Time Frame: Baseline to Week 61]

Change From Baseline in Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Motor Skills Domain Score [Time Frame: Baseline to Week 61]

Change From Baseline in Alexander Disease Patient Domain Impression of Change (AxD-PDIC) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Cerebrospinal Fluid (CSF) Glial Fibrillary Acid Protein (GFAP) Levels [Time Frame: Baseline and Week 61]

Change From Baseline in Alexander Disease Patient Domain Impression of Severity (AxD-PDIS) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Gross Motor Function Measure-88, Dimensions C, D and E (GMFM-88, Dimensions C-E) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Composite Autonomic Symptom Score 31 (COMPASS-31) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Patient Global Impression of Severity (PGIS) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Most Bothersome Symptom (MBS) [Time Frame: Baseline and Week 61]

Change From Baseline in Clinical Global Impression of Severity (CGIS) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Body Weight Percentile (for participants < 18 years old at screening) or body weight (for participants = 18 years old at screening) [Time Frame: Baseline and Week 61]

Change From Baseline in Clinical Global Impression of Change (CGIC) Score [Time Frame: Baseline and Week 61]

Change From Baseline in Vineland Adaptive Behavior Composite, Third Edition (Vineland-3 ABC) Score [Time Frame: Baseline to Week 61]

Secondary ID(s)

2024-510603-11-00

ION373-CS1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors